Mortality from acute respiratory distress syndrome(ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only....Mortality from acute respiratory distress syndrome(ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation(APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury(ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.展开更多
Maintaining adequate oxygenation during one-lung ventilation(OLV) requires high inspired oxygen fraction(FiO_2).However,high FiO_2 also causes inflammatory response and lung injury.Therefore,it remains a great int...Maintaining adequate oxygenation during one-lung ventilation(OLV) requires high inspired oxygen fraction(FiO_2).However,high FiO_2 also causes inflammatory response and lung injury.Therefore,it remains a great interest to clinicians and scientists to optimize the care of patients undergoing OLV.The aim of this study was to determine and compare oxygenation,inflammatory response and lung injury during OLV in rabbits using FiO_2 of 0.6 vs.1.0.After 30 minutes of two-lung ventilation(TLV) as baseline,30 rabbits were randomly assigned to three groups receiving mechanical ventilation for 3 hours:the sham group,receiving TLV with 0.6 FiO_2;the 1.0 FiO_2 group,receiving OLV with 1.0 FiO_2;the 0.6 FiO_2 group,receiving OLV with 0.6 FiO_2.Pulse oximetry was continuously monitored and arterial blood gas analysis was intermittently conducted.Histopathologic study of lung tissues was performed and inflammatory cytokines and the mRNA and protein of nuclear factor kappa B(NF-κB) p65 were determined.Three of the 10 rabbits in the 0.6 FiO_2 group suffered hypoxemia,defined by pulse oximetric saturation(SpO_2) less than 90%.Partial pressure of oxygen(PaO_2),acute lung injury(ALI) score,myeloperoxidase(MPO),tumor necrosis factor-a(TNF-α),interleukin-6(IL-6),mRNA and protein of NF-kB p65 were lower in the 0.6 FiO_2group than in the 1.0 FiO_2 group.In conclusion,during OLV,if FiO_2 of 0.6 can be tolerated,lung injury associated with high FiO_2 can be minimized.Further study is needed to validate this finding in human subjects.展开更多
We investigated the effects of zinc deficiency on acute lung injury (ALI) induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then rece...We investigated the effects of zinc deficiency on acute lung injury (ALI) induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then received mechanical ventilation at normal frequency and pressure for 30 min. Total protein, cell count, the number of poly- morphonuclear neutrophil (PMN) in the bronchoalveolar lavage (BAL), and vascular endothelial growth factor (VEGF) expression in the lung were determined. Activation of nuclear factor-t^B (NF-~cB) was detected by exam- ining the phosphorylation of NF-kB (pNF-kB p65) and the expression of inhibitor of NF-kB (pI-kBa). Compared to the controls, total cell count and the number of PMNs were significantly increased to 160% and 140%, respec- tively, in zinc-deficient rats treated with ventilation. Activation of NF-kB was significantly increased and VEGF was also increased to three-folds. Zinc deficiency aggravated the inflammatory response in rats and was associated with the overexpression of VEGF in response to mechanical ventilation. Zinc supplementation may be beneficial to zinc-deficient patients during mechanical ventilation.展开更多
Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats ...Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats were randomly divided into low tidal volume ventilation group (Vt: 7 mL/kg, LV group) or high tidal volume ventilation group (Vt:42mL/kg, HV group ) (n=40 in each). Rats in each group were ventilated for 0, 60, 90, 120 and 240 min. The wet/dry lung weight ratio (W/D) was measured. The levels of macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α), and the activity of myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). The number of neutrophils in bronchoalveolar lavage fluid (BALF) was counted after Wright’s staining, and the percentage of netrophils in lung tissues calculated. Histopatholgical examination was used to observe the changes of lung tissues after different ventilations. The results showed that the W/D weight ratio was increased, and the levels of MIP-2 and TNF-α significantly enhanced in HV group at 90, 120 and 240 min. Neutrophils in BALF and the neutrophil percentage in lung tissues were also elevated at 120 and 240 min, which coincided with the enhanced activity of MPO in HV group. The lung injury was significantly related with the ventilation time and the infiltration of neutrophils in lungs in HV group. In conclusion, in ventilation-induced lung injury, neutrophil infiltration is present in a time-dependent manner and associated with the aggravated lung injury. Pulmonary structural damage may be the main reason for ventilation-induced lung injury.展开更多
Objective: To study the effect of the adaptive intermittent ventilation before radical operation for lung cancer under one-lung ventilation on non-ventilated lung tissue injury and apoptosis molecule protein expressio...Objective: To study the effect of the adaptive intermittent ventilation before radical operation for lung cancer under one-lung ventilation on non-ventilated lung tissue injury and apoptosis molecule protein expression. Methods: A total of 288 patients who received radical operation for lung cancer in the hospital between February 2015 and January 2017 were divided into control group and observation group by random number table method, each with 144 cases. Control group received routine one-lung ventilation, and observation group received preoperative adaptive intermittent ventilation of non-ventilated lung tissue. The differences in the levels of inflammatory factors and oxidative stress indexes in serum as well as the apoptosis molecule protein expression in affected-side normal lung tissue were compared between the two groups of patients immediately after intubation and at two-lung ventilation (T0) as well as 10 min before operation ended and at one-lung ventilation (T1). Results: At T0, the differences in the levels of inflammatory factors and oxidative stress indexes in serum as well as the apoptosis molecule protein expression in affected-side normal lung tissue were not significantly significant between the two groups of patients;at T1, IL-1β, IL-8, TNF-α, MPO and MDA levels in serum as well as Bax, caspase-2 and caspase-3 protein expression in normal lung tissue of observation group were lower than those of control group while SOD level in serum and Bcl-2 protein expression in normal lung tissue were higher than those of control group. Conclusion: Adaptive intermittent ventilation before radical operation for lung cancer under one-lung ventilation can effectively reduce the non-ventilated lung tissue injury and inhibit the apoptosis of normal lung cells.展开更多
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indir...Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.展开更多
Expiratory flow limitation(EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety...Expiratory flow limitation(EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety of intensive care unit conditions. Recent evidence suggests that the presence of EFL is associated with an increase in mortality, at least in acute respiratory distress syndrome(ARDS) patients, and in pulmonary complications in patients undergoing surgery. EFL is a major cause of intrinsic positive end-expiratory pressure(PEEPi), which in ARDS patients is heterogeneously distributed, with a consequent increase of ventilation/perfusion mismatch and reduction of arterial oxygenation. Airway collapse is frequently concomitant to the presence of EFL.When airways close and reopen during tidal ventilation, abnormally high stresses are generated that can damage the bronchiolar epithelium and uncouple small airways from the alveolar septa, possibly generating the small airways abnormalities detected at autopsy in ARDS. Finally, the high stresses and airway distortion generated downstream the choke points may contribute to parenchymal injury, but this possibility is still unproven. PEEP application can abolish EFL, decrease PEEPi heterogeneity, and limit recruitment/derecruitment.Whether increasing PEEP up to EFL disappearance is a useful criterion for PEEP titration can only be determined by future studies.展开更多
The expression changes of early response genes due to ventilation with high volume in adult rats in vivo were observed. Forty SD male rats were randomly divided into control and 30, 60, 90 and 120 min ventilation grou...The expression changes of early response genes due to ventilation with high volume in adult rats in vivo were observed. Forty SD male rats were randomly divided into control and 30, 60, 90 and 120 min ventilation groups, respectively (n=8 in each group). The animals were ventilated with tidal volume of 42 ml/kg and a PEEP level of 0 cmH_2O at a rate of 40 breaths per minute in room air with a ventilator was given to the small animals. The expression of Egr-1, C-jun and IL-1β mRNA and proteins was detected by RT-PCR and immunohistochemical technique, respectively. The pathological changes in lung tissues were examined by HE staining. The results indicated that the expression of Egr-1, C-jun and IL-1β mRNA was detectable at 30th min after overventilation, but there was no significant difference in comparison with that in control group until overventilation for 60 min. However, at 90 and 120 min there was a significent increase as compared with 30 min or control group (P<0.05). The expression of Egr-1, C-jun and IL-1β deteced by immunohistochemical assay also showed a similar tendency of the gradual increase. In the 120 min ventilation group, the expression intensity of Egr-1, C-jun and IL-1β proteins in lung cells was the strongest and the nuclear translocation was increased markedly in comparison with any other groups (P<0.05). HE staining suggested that the degree of lung injury was aggravated gradually with the ventialtion going on and had a similar tendency to the expression of these early response genes and proteins. The current data suggested that overventilation activated and upregulated the expression of early response genes and the expression of these genes may be taken as the early signal to predict the onset and degree of lung injury. These results may demonstrated partially that the expression of early response genes induced by the mechanical stretch is associated with biochamic lung injury.展开更多
BACKGROUND:Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome(ARDS) including lung injury,and systemic inflammatory response high tidal volumes are thought to increase mortality.The ...BACKGROUND:Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome(ARDS) including lung injury,and systemic inflammatory response high tidal volumes are thought to increase mortality.The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries(VILI) and to explore its potential mechanisms.METHODS:Thirty-six healthy dogs were randomly divided into a control group and an experimental group.Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow.Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α.Lung tissue specimens were also extracted for total RNA,IL-8 by western blot and observed under an electronic microscope.RESULTS:IL-8 protein expression was significantly higher in group B than in groups A and D.Although the IL-8 protein expression was decreased in group C compared with group B,the difference was not statistically significant.The TNF-α ray degree of group B was significantly higher than that in the other groups(P<0.01),especially in group C(P>0.05).The alveolar volume of subjects in group B was significantly smaller,and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa,disorder of interval structures,and blurring of collagenous and elastic fiber structures.A large number of necrotic debris tissue was observed in group B.CONCLUSION:Mechanical ventilation with a large tidal volume,a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure.It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression.Furthermore,the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media.This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.展开更多
Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathologi...Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathological obstetrics. ALI and ARDS demonstrate similar pathophysiological changes. The severe stage of ALI is defined as ARDS. At present, a significant progress has been achieved in the study of the pathogenesis and pathophysiology of ALI/ARDS. Whether or not ALI/ARDS patients can recover depends on the degree of lung injury, extra-pulmonary organ damage, original primary disease of a patient, and adequacy in supportive care. Conservative infusion strategies and protective lung ventilation reduce ARDS disability and mortality. In this study, the pathogenesis of ALI/ARDS, lung injury, molecular mechanisms of lung repair, and conservative infusion strategies and pulmonary protective ventilation are reviewed comprehensively.展开更多
BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory d...BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory distress syndrome (ARDS).METHODS: ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilatedwith neurally adjusted ventilatory assistance (NAVA) with a tidal volume (VT) of 6 mL/kg and theelectrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation ofthe bilateral vagus nerve trunk, the rabbits were randomized into two groups: sham operation (SHAM)group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanicswere detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively.Pulmonary permeability index, pathological changes and infl ammatory response were also measured.RESULTS: Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased signifi cantly2 and 3 hours after ventilation (P〈0.05). There was no significant difference in PaCO2 betweenthe SHAM and VAG groups (P〉0.05), and the VAG group had a high VT, peak pressure (Ppeak),and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P〈0.05).Compared to the SHAM group, dead space fraction (VD/VT) and respiratory system elastance (Ers)in the VAG group increased (P〈0.05) and static pulmonary compliance (Cst) decreased markedly(P〈0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injuryscore (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-# (TNF-#) (779±372 pg/mL vs. 355±130 pg/mL)and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG groupcompared with the SHAM group (P〈0.05).CONCLUSION: Lung injury is aggravated after bilateral vagotomy, demonstrating thatpulmonary stretch refl ex may have protective effect on the lung.展开更多
Driving pressure(ΔP)is a core therapeutic component of mechanical ventilation(MV).Varying levels ofΔP have been employed during MV depending on the type of underlying pathology and severity of injury.However,ΔP lev...Driving pressure(ΔP)is a core therapeutic component of mechanical ventilation(MV).Varying levels ofΔP have been employed during MV depending on the type of underlying pathology and severity of injury.However,ΔP levels have also been shown to closely impact hard endpoints such as mortality.Considering this,conducting an in-depth review ofΔP as a unique,outcome-impacting therapeutic modality is extremely important.There is a need to understand the subtleties involved in making sureΔP levels are optimized to enhance outcomes and minimize harm.We performed this narrative review to further explore the various uses ofΔP,the different parameters that can affect its use,and how outcomes vary in different patient populations at different pressure levels.To better utilizeΔP in MV-requiring patients,additional large-scale clinical studies are needed.展开更多
Independent lung ventilation,though infrequently used in the critical care setting,has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology.This involv...Independent lung ventilation,though infrequently used in the critical care setting,has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology.This involves isolating and ventilating the right and left lung differently,using separate ventilators.Here,we describe our experience with independent lung ventilation in a patient with unilateral diffuse alveolar hemorrhage,who presented with severe hypoxemic respiratory failure despite maximal ventilatory support.Conventional ventilation in this scenario leads to preferential distribution of tidal volume to the nondiseased lung causing over distension and inadvertent volume trauma.Since each lung has a different compliance and respiratory mechanics,instituting separate ventilation strategies to each lung could potentially minimize lung injury.Based on review of literature,we provide a detailed description of indications and procedures for establishing independent lung ventilation,and also provide an algorithm for management and weaning a patient from independent lung ventilation.展开更多
Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured p...Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured patients because respiratory failure and mechanical ventilation seem to be a risk factor for increased mortality, poor neurological outcome and longer intensive care unit or hospital length of stay. Brain and lung strongly interact via complex pathways from the brain to the lung but also from the lung to the brain. Several hypotheses have been proposed with a particular interest for the recently described "double hit" model. Ventilator setting in brain-injured patients with lung injuries has been poorly studied and intensivists are often fearful to use some parts of protective ventilation in patients with brain injury. This review aims to describe the epidemiology and pathophysiology of lung injuries in brain-injured patients, but also the impact of different modalities of mechanical ventilation on the brain in the context of acute brain injury.展开更多
The lung plays a vital role in maintaining homeostasis,as it is responsible for the exchange of oxygen and carbon dioxide.Pulmonary homeostasis is maintained by a network of tissue-resident cells,including epithelial ...The lung plays a vital role in maintaining homeostasis,as it is responsible for the exchange of oxygen and carbon dioxide.Pulmonary homeostasis is maintained by a network of tissue-resident cells,including epithelial cells,endothelial cells and leukocytes.Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung.Recently developed unbiased next generation sequencing(NGS)has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge.New phenotypes and distinct gene signatures have been identified,and these new findings enhance the diagnosis and treatment of lung diseases.Here,we present a review of the new NGS findings on myeloid cells in lung development,homeostasis,and lung diseases,including acute lung injury(ALI),lung fibrosis,chronic obstructive pulmonary disease(COPD),and lung cancer.展开更多
Acute Respiratory Distress Syndrome (ARDS) is a major cause of morbidity and has a high rate of mortality. ARDS patients in the intensive care unit (ICU) require mechan-ical ventilation (MV) for breathing support, but...Acute Respiratory Distress Syndrome (ARDS) is a major cause of morbidity and has a high rate of mortality. ARDS patients in the intensive care unit (ICU) require mechan-ical ventilation (MV) for breathing support, but inappropriate settings of MV can lead to ventilator induced lung injury (VILI). Those complications may be avoided by carefully optimizing ventilation parameters through model-based approaches. In this study we introduced a new model of lung mechanics (mNARX) which is a variation of the NARX model by Langdon et al. A multivariate process was undertaken to deter-mine the optimal parameters of the mNARX model and hence, the final structure of the model fit 25 patient data sets and successfully described all parts of the breathing cycle. The model was highly successful in predicting missing data and showed minimal error. Thus, this model can be used by the clinicians to find the optimal patient specific ventilator settings.展开更多
文摘Mortality from acute respiratory distress syndrome(ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation(APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury(ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.
基金supported by grants from Department of Anesthesiology,Jiangsu Cancer Hospital
文摘Maintaining adequate oxygenation during one-lung ventilation(OLV) requires high inspired oxygen fraction(FiO_2).However,high FiO_2 also causes inflammatory response and lung injury.Therefore,it remains a great interest to clinicians and scientists to optimize the care of patients undergoing OLV.The aim of this study was to determine and compare oxygenation,inflammatory response and lung injury during OLV in rabbits using FiO_2 of 0.6 vs.1.0.After 30 minutes of two-lung ventilation(TLV) as baseline,30 rabbits were randomly assigned to three groups receiving mechanical ventilation for 3 hours:the sham group,receiving TLV with 0.6 FiO_2;the 1.0 FiO_2 group,receiving OLV with 1.0 FiO_2;the 0.6 FiO_2 group,receiving OLV with 0.6 FiO_2.Pulse oximetry was continuously monitored and arterial blood gas analysis was intermittently conducted.Histopathologic study of lung tissues was performed and inflammatory cytokines and the mRNA and protein of nuclear factor kappa B(NF-κB) p65 were determined.Three of the 10 rabbits in the 0.6 FiO_2 group suffered hypoxemia,defined by pulse oximetric saturation(SpO_2) less than 90%.Partial pressure of oxygen(PaO_2),acute lung injury(ALI) score,myeloperoxidase(MPO),tumor necrosis factor-a(TNF-α),interleukin-6(IL-6),mRNA and protein of NF-kB p65 were lower in the 0.6 FiO_2group than in the 1.0 FiO_2 group.In conclusion,during OLV,if FiO_2 of 0.6 can be tolerated,lung injury associated with high FiO_2 can be minimized.Further study is needed to validate this finding in human subjects.
文摘We investigated the effects of zinc deficiency on acute lung injury (ALI) induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then received mechanical ventilation at normal frequency and pressure for 30 min. Total protein, cell count, the number of poly- morphonuclear neutrophil (PMN) in the bronchoalveolar lavage (BAL), and vascular endothelial growth factor (VEGF) expression in the lung were determined. Activation of nuclear factor-t^B (NF-~cB) was detected by exam- ining the phosphorylation of NF-kB (pNF-kB p65) and the expression of inhibitor of NF-kB (pI-kBa). Compared to the controls, total cell count and the number of PMNs were significantly increased to 160% and 140%, respec- tively, in zinc-deficient rats treated with ventilation. Activation of NF-kB was significantly increased and VEGF was also increased to three-folds. Zinc deficiency aggravated the inflammatory response in rats and was associated with the overexpression of VEGF in response to mechanical ventilation. Zinc supplementation may be beneficial to zinc-deficient patients during mechanical ventilation.
基金supported by a grant from the Natural Science Foundation of Shandong Province of China(No.Y2007C119)
文摘Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats were randomly divided into low tidal volume ventilation group (Vt: 7 mL/kg, LV group) or high tidal volume ventilation group (Vt:42mL/kg, HV group ) (n=40 in each). Rats in each group were ventilated for 0, 60, 90, 120 and 240 min. The wet/dry lung weight ratio (W/D) was measured. The levels of macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α), and the activity of myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). The number of neutrophils in bronchoalveolar lavage fluid (BALF) was counted after Wright’s staining, and the percentage of netrophils in lung tissues calculated. Histopatholgical examination was used to observe the changes of lung tissues after different ventilations. The results showed that the W/D weight ratio was increased, and the levels of MIP-2 and TNF-α significantly enhanced in HV group at 90, 120 and 240 min. Neutrophils in BALF and the neutrophil percentage in lung tissues were also elevated at 120 and 240 min, which coincided with the enhanced activity of MPO in HV group. The lung injury was significantly related with the ventilation time and the infiltration of neutrophils in lungs in HV group. In conclusion, in ventilation-induced lung injury, neutrophil infiltration is present in a time-dependent manner and associated with the aggravated lung injury. Pulmonary structural damage may be the main reason for ventilation-induced lung injury.
文摘Objective: To study the effect of the adaptive intermittent ventilation before radical operation for lung cancer under one-lung ventilation on non-ventilated lung tissue injury and apoptosis molecule protein expression. Methods: A total of 288 patients who received radical operation for lung cancer in the hospital between February 2015 and January 2017 were divided into control group and observation group by random number table method, each with 144 cases. Control group received routine one-lung ventilation, and observation group received preoperative adaptive intermittent ventilation of non-ventilated lung tissue. The differences in the levels of inflammatory factors and oxidative stress indexes in serum as well as the apoptosis molecule protein expression in affected-side normal lung tissue were compared between the two groups of patients immediately after intubation and at two-lung ventilation (T0) as well as 10 min before operation ended and at one-lung ventilation (T1). Results: At T0, the differences in the levels of inflammatory factors and oxidative stress indexes in serum as well as the apoptosis molecule protein expression in affected-side normal lung tissue were not significantly significant between the two groups of patients;at T1, IL-1β, IL-8, TNF-α, MPO and MDA levels in serum as well as Bax, caspase-2 and caspase-3 protein expression in normal lung tissue of observation group were lower than those of control group while SOD level in serum and Bcl-2 protein expression in normal lung tissue were higher than those of control group. Conclusion: Adaptive intermittent ventilation before radical operation for lung cancer under one-lung ventilation can effectively reduce the non-ventilated lung tissue injury and inhibit the apoptosis of normal lung cells.
文摘Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.
文摘Expiratory flow limitation(EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety of intensive care unit conditions. Recent evidence suggests that the presence of EFL is associated with an increase in mortality, at least in acute respiratory distress syndrome(ARDS) patients, and in pulmonary complications in patients undergoing surgery. EFL is a major cause of intrinsic positive end-expiratory pressure(PEEPi), which in ARDS patients is heterogeneously distributed, with a consequent increase of ventilation/perfusion mismatch and reduction of arterial oxygenation. Airway collapse is frequently concomitant to the presence of EFL.When airways close and reopen during tidal ventilation, abnormally high stresses are generated that can damage the bronchiolar epithelium and uncouple small airways from the alveolar septa, possibly generating the small airways abnormalities detected at autopsy in ARDS. Finally, the high stresses and airway distortion generated downstream the choke points may contribute to parenchymal injury, but this possibility is still unproven. PEEP application can abolish EFL, decrease PEEPi heterogeneity, and limit recruitment/derecruitment.Whether increasing PEEP up to EFL disappearance is a useful criterion for PEEP titration can only be determined by future studies.
基金This project was supported by a grant from National Edu-cational Ministry (No .20020487063) and National NaturalSciences Foundation of China (No .30471661) .
文摘The expression changes of early response genes due to ventilation with high volume in adult rats in vivo were observed. Forty SD male rats were randomly divided into control and 30, 60, 90 and 120 min ventilation groups, respectively (n=8 in each group). The animals were ventilated with tidal volume of 42 ml/kg and a PEEP level of 0 cmH_2O at a rate of 40 breaths per minute in room air with a ventilator was given to the small animals. The expression of Egr-1, C-jun and IL-1β mRNA and proteins was detected by RT-PCR and immunohistochemical technique, respectively. The pathological changes in lung tissues were examined by HE staining. The results indicated that the expression of Egr-1, C-jun and IL-1β mRNA was detectable at 30th min after overventilation, but there was no significant difference in comparison with that in control group until overventilation for 60 min. However, at 90 and 120 min there was a significent increase as compared with 30 min or control group (P<0.05). The expression of Egr-1, C-jun and IL-1β deteced by immunohistochemical assay also showed a similar tendency of the gradual increase. In the 120 min ventilation group, the expression intensity of Egr-1, C-jun and IL-1β proteins in lung cells was the strongest and the nuclear translocation was increased markedly in comparison with any other groups (P<0.05). HE staining suggested that the degree of lung injury was aggravated gradually with the ventialtion going on and had a similar tendency to the expression of these early response genes and proteins. The current data suggested that overventilation activated and upregulated the expression of early response genes and the expression of these genes may be taken as the early signal to predict the onset and degree of lung injury. These results may demonstrated partially that the expression of early response genes induced by the mechanical stretch is associated with biochamic lung injury.
基金supported by grants from the Shanghai Health Bureau issues(2007102)
文摘BACKGROUND:Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome(ARDS) including lung injury,and systemic inflammatory response high tidal volumes are thought to increase mortality.The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries(VILI) and to explore its potential mechanisms.METHODS:Thirty-six healthy dogs were randomly divided into a control group and an experimental group.Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow.Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α.Lung tissue specimens were also extracted for total RNA,IL-8 by western blot and observed under an electronic microscope.RESULTS:IL-8 protein expression was significantly higher in group B than in groups A and D.Although the IL-8 protein expression was decreased in group C compared with group B,the difference was not statistically significant.The TNF-α ray degree of group B was significantly higher than that in the other groups(P<0.01),especially in group C(P>0.05).The alveolar volume of subjects in group B was significantly smaller,and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa,disorder of interval structures,and blurring of collagenous and elastic fiber structures.A large number of necrotic debris tissue was observed in group B.CONCLUSION:Mechanical ventilation with a large tidal volume,a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure.It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression.Furthermore,the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media.This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.
文摘Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathological obstetrics. ALI and ARDS demonstrate similar pathophysiological changes. The severe stage of ALI is defined as ARDS. At present, a significant progress has been achieved in the study of the pathogenesis and pathophysiology of ALI/ARDS. Whether or not ALI/ARDS patients can recover depends on the degree of lung injury, extra-pulmonary organ damage, original primary disease of a patient, and adequacy in supportive care. Conservative infusion strategies and protective lung ventilation reduce ARDS disability and mortality. In this study, the pathogenesis of ALI/ARDS, lung injury, molecular mechanisms of lung repair, and conservative infusion strategies and pulmonary protective ventilation are reviewed comprehensively.
文摘BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory distress syndrome (ARDS).METHODS: ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilatedwith neurally adjusted ventilatory assistance (NAVA) with a tidal volume (VT) of 6 mL/kg and theelectrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation ofthe bilateral vagus nerve trunk, the rabbits were randomized into two groups: sham operation (SHAM)group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanicswere detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively.Pulmonary permeability index, pathological changes and infl ammatory response were also measured.RESULTS: Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased signifi cantly2 and 3 hours after ventilation (P〈0.05). There was no significant difference in PaCO2 betweenthe SHAM and VAG groups (P〉0.05), and the VAG group had a high VT, peak pressure (Ppeak),and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P〈0.05).Compared to the SHAM group, dead space fraction (VD/VT) and respiratory system elastance (Ers)in the VAG group increased (P〈0.05) and static pulmonary compliance (Cst) decreased markedly(P〈0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injuryscore (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-# (TNF-#) (779±372 pg/mL vs. 355±130 pg/mL)and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG groupcompared with the SHAM group (P〈0.05).CONCLUSION: Lung injury is aggravated after bilateral vagotomy, demonstrating thatpulmonary stretch refl ex may have protective effect on the lung.
文摘Driving pressure(ΔP)is a core therapeutic component of mechanical ventilation(MV).Varying levels ofΔP have been employed during MV depending on the type of underlying pathology and severity of injury.However,ΔP levels have also been shown to closely impact hard endpoints such as mortality.Considering this,conducting an in-depth review ofΔP as a unique,outcome-impacting therapeutic modality is extremely important.There is a need to understand the subtleties involved in making sureΔP levels are optimized to enhance outcomes and minimize harm.We performed this narrative review to further explore the various uses ofΔP,the different parameters that can affect its use,and how outcomes vary in different patient populations at different pressure levels.To better utilizeΔP in MV-requiring patients,additional large-scale clinical studies are needed.
文摘Independent lung ventilation,though infrequently used in the critical care setting,has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology.This involves isolating and ventilating the right and left lung differently,using separate ventilators.Here,we describe our experience with independent lung ventilation in a patient with unilateral diffuse alveolar hemorrhage,who presented with severe hypoxemic respiratory failure despite maximal ventilatory support.Conventional ventilation in this scenario leads to preferential distribution of tidal volume to the nondiseased lung causing over distension and inadvertent volume trauma.Since each lung has a different compliance and respiratory mechanics,instituting separate ventilation strategies to each lung could potentially minimize lung injury.Based on review of literature,we provide a detailed description of indications and procedures for establishing independent lung ventilation,and also provide an algorithm for management and weaning a patient from independent lung ventilation.
基金Acknowledgements This study was supported by the National Natural Science Foundation of China (Grant No.30772085) and graduate innovation fund of Heilongjiang Province.
文摘Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured patients because respiratory failure and mechanical ventilation seem to be a risk factor for increased mortality, poor neurological outcome and longer intensive care unit or hospital length of stay. Brain and lung strongly interact via complex pathways from the brain to the lung but also from the lung to the brain. Several hypotheses have been proposed with a particular interest for the recently described "double hit" model. Ventilator setting in brain-injured patients with lung injuries has been poorly studied and intensivists are often fearful to use some parts of protective ventilation in patients with brain injury. This review aims to describe the epidemiology and pathophysiology of lung injuries in brain-injured patients, but also the impact of different modalities of mechanical ventilation on the brain in the context of acute brain injury.
基金the USA National Institutes of Health Grant R01-HL-079669(J.F.)USA National Institutes of Health Grant R01HL076179(J.F.)+2 种基金USA National Institutes of Health Grant R01HL-139547(J.F.)VA Merit Award 1I01BX002729(J.F.)VA BLR&D Award 1IK6BX004211(J.F.).
文摘The lung plays a vital role in maintaining homeostasis,as it is responsible for the exchange of oxygen and carbon dioxide.Pulmonary homeostasis is maintained by a network of tissue-resident cells,including epithelial cells,endothelial cells and leukocytes.Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung.Recently developed unbiased next generation sequencing(NGS)has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge.New phenotypes and distinct gene signatures have been identified,and these new findings enhance the diagnosis and treatment of lung diseases.Here,we present a review of the new NGS findings on myeloid cells in lung development,homeostasis,and lung diseases,including acute lung injury(ALI),lung fibrosis,chronic obstructive pulmonary disease(COPD),and lung cancer.
文摘Acute Respiratory Distress Syndrome (ARDS) is a major cause of morbidity and has a high rate of mortality. ARDS patients in the intensive care unit (ICU) require mechan-ical ventilation (MV) for breathing support, but inappropriate settings of MV can lead to ventilator induced lung injury (VILI). Those complications may be avoided by carefully optimizing ventilation parameters through model-based approaches. In this study we introduced a new model of lung mechanics (mNARX) which is a variation of the NARX model by Langdon et al. A multivariate process was undertaken to deter-mine the optimal parameters of the mNARX model and hence, the final structure of the model fit 25 patient data sets and successfully described all parts of the breathing cycle. The model was highly successful in predicting missing data and showed minimal error. Thus, this model can be used by the clinicians to find the optimal patient specific ventilator settings.